The project extends the attempts to define biologically, genetically, diagnostically and therapeutically distinct subgroups of the schizophrenic-like illnesses. Recent studies have suggested that multimodal distributions of certain key biological findings occur in schizophrenic populations while unimodal distributions of similar parameters occur in control populations. These biologic multimodalities (platelet MAO activity, growth hormone response to apomorphine, membrane ion conterflow deficiencies) together with symptom change distributions following physostigmine challenges and lithium treatment provide the basis for investigations of different genetic, diagnostic and treatment response groups. Each of 80 patients diagnosed as schizophrenia or schizoaffective disorder (RDC) is undergoing biologic testing on the parameters noted above before receiving a physostigmine challenge and a two week lithium trial with close monitoring for symptom change. First degree relatives of all patients are being studied for evidence of diagnosable (SADS-L) illness. Data analysis will determine whether a subgroup of the schizophrenic-like population can be defined which manifests characteristic patterns of abnormalities by biological testing, characteristic patterns of illness in first degree family members, characteristic life history or symptom cluster features which predict antipsychotic response to lithium. The delineation by multivariate, cluster analysis of such a subgroup of the schizophrenic-like population is the goal of the proposed work.